The present invention pertains to the formation of an hydroxyaromatic ketoacetal from an hydroxyaromatic methylketone, to the formation of hydroxyaromatic ketoaldehyde from an hydroxyaromatic ketoacetal, and further to the formation of an hydantoin from the hydroxyaromatic ketoaldehyde. The invention also pertains to subsequent hydrolysis of the hydantoin to produce a hydroxyphenylglycine, and to techniques for resolution of optical isomers to provide a D-hydroxyphenylglycine.
In particular, the present invention relates to an improved process for the production of hydantoins and glycines. More particularly, the invention relates to a process for the preparation of 5-(4'-hydroxyphenyl)hydantoin and p-hydroxyphenylglycine, and to the resolution of D-p-hydroxyphenylglycine, wherein the starting material for production of the hydantoins is 4-hydroxyacetophenone.
5-(4'-Hydroxyphenyl)hydantoin is an important intermediate in the production of D-4-hydroxyphenylglycine which is employed for preparing semi-synthetic penicillins and cephalosporins. It is known that 5-(4'-hydroxyphenyl)-hydantoin may be synthesized by the reaction of 4-hydroxybenzaldehyde, ammonium bicarbonate and sodium cyanide according to Bucherer-Berg's method. However, this method requires the use of dangerous sodium cyanide, and further, the obtained crude hydantoin may contain large quantities of by-products caused by the oxidative side reaction of the phenol nucleus under an alkaline condition or may be colored.
U.S. Pat. No. 4,230,869 provides a process for preparing 5-(4'-hydroxyphenyl)hydantoin by reacting glyoxylic acid, urea and phenol in the presence of an acid. One disadvantage of this method is the requirement of heating to 40.degree. to 100.degree. to drive the reaction. 5-(4'-Hydroxyphenyl)hydantoins have also been prepared by reacting allantoin with phenol in the presence of acids as taught in Japanese Kokai 78/112874.
In the prior art, D-4-hydroxyphenylglycine has been generally prepared by chemically subjecting DL-4-hydroxyphenylglycine to optical resolution. However, such a process has the disadvantage that DL-4hydroxyphenylglycine must be converted to derivatives such as esterification and acylation products prior to subjecting it to optical resolution, or resolving reagents are required, and also process steps are required for racemizing the residual L-form.
It is also known in the art that D-4-hydroxyphenylglycine may be prepared by the enzymatic or alkali hydrolysis of 5-(4'-hydroxyphenyl)hydantoin. In this regard one may refer to Takehashi, Microbial Production of D-p-Hydroxyphenylglycine, Prog. Ind. Microbiol. 24(Biotechnol. Amino Acid Prod.) 269-79 (1896) and U.S. Pat. No. 4,436,510 which are incorporated herein by reference.
In U.S. Pat. No. 3,094,741, which is incorporated herein by reference, it is disclosed that DL-5-(4-hydroxyphenyl)hydantoin can be almost quantitatively converted to D-N-carbamoyl-(4-hydroxyphenyl)glycine by causing cells or treated cells of specific microorganisms to act on the hydantoin in an aqueous medium at pH 7 to 10. D-N-carbamoyl-(4-hydroxyphenyl)glycine can be converted into D-4-hydroxyphenylglycine in high yields, for instance by reacting it with an equimolar amount of nitrous acid in the presence of a strong acid.